1. The Audiology Unit continued our protocol designed to develop normative data for various aspects of auditory and vestibular function. This data is used to establish normal reference ranges for test interpretation and control data for comparison to results obtained for various patient groups in our collaborative research endeavors. We are also examining the effects of various methodologies, stimulus characteristics, test equipment, and subject characteristics (e.g., age, sex) on normal function, and are evaluating variability of auditory and vestibular measures over time. During this past year we conducted a study examining the algorithms used to interpret postural stability on Computerized Platform Posturography. This work will be presented at a national meeting in Spring 2020 and we are currently working on manuscript development (Wafa et al.). Additionally, we published a manuscript based on earlier work that compared methods for quantifying utricular function (Zalewski et al., 2018). 2. In collaboration with other NIH investigators (NHLBI, NIAID and NCI), we continue our comprehensive monitoring program for persons participating in clinical trials in which there may be risk of ototoxic hearing loss. These include aminoglycosides, anti-neoplastic compounds, and radiation therapy for brain tumors. In concert with our focus on ototoxicity, we published an article (Brewer & King, 2018) on ototoxicity grading scales, and co-edited (Brewer & Boudin, 2018) a special edition of the International J. of Audiology devoted to the topic of clinical ototoxicity monitoring. We presented a poster on amikacin ototoxicity at the American Auditory Society meeting (Chisholm et al., 2019) and are scheduled to present additional work in this area at an upcoming conference (NCRAR). 3. We designed and completed a test protocol to determine the stability of the auditory nerve action potential and otoacoustic emissions in a group of healthy volunteers. The goals were to determine feasibility of these physiologic measures as markers of damage to the auditory system from noise or ototoxic agents (Bieber et al., manuscript in submission) and to determine hearing safety following prolonged exposure to MRI noise while using hearing protection in support of research being conducted by Drs. Duyn & Picchioni (NINDS). We contributed to a manuscript that includes hearing safety data (Moehlman et al, 2019). 4. In collaboration with Dr. Griffith (NIDCD), we continued auditory and vestibular phenotypic assessments of individuals with enlarged vestibular aqueducts (EVA) as well as their siblings and parents. To date, over 100 probands and their families have been ascertained. We are co-authors on a manuscript examining the influence of the SLC26A4 haplotype on the phenotype of persons with EVA (Chao et al., 2019). 5. In collaboration with Dr. Williamson (NIAID), we have evaluated and characterized auditory function in a group of previously healthy patients with cryptococcal meningitis (King et al., 2019). 6. In collaboration with Dr. Porter (NICHD), we continue participation in a phase 2/3a-c trial of hydroxypropyl beta cyclodextrin for treatment of Niemann Pick type C disease. Our roles included auditory monitoring, ototoxicity grading, and reporting to FDA and safety monitors. 7. In collaboration with (Porter, NICHD) we have examined auditory function in patients with Smith-Lemli-Opitz syndrome. A manuscript is being developed (Zalewski et al., in preparation). 8. We are conducting a detailed cross-sectional and longitudinal examination of hereditary hearing loss and auditory function in persons with neurofibromatosis type I (NF1) (Widemann, NCI). This work was presented at the ASHA meeting in November 2018 and a manuscript is being developed (Idowu et al., in preparation). 9. In collaboration with Dr. McDermott (NIAID), we analyzed auditory function in persons with WHIM syndrome; this work was presented at the AA0-HNS meeting in October 2018 (Rieger et al.). 10. In collaboration with Drs. Friedman & Griffith (NIDCD) and Dr. Zein (NEI), we continue to study hearing and balance function in persons with Usher syndrome. We are interested in postural balance skills and their relationship to vestibular and visual function, type of Usher syndrome, genotype, and the progression/decline of these skills over time. We have two manuscript in preparation: one that details comprehensive balance function in the three types of Usher syndrome. (Wafa et al.) and another that reviews the classification of atypical Usher syndrome (Zein et al.). 11. In collaboration with Dr. Goldbach-Mansky (NIAMS) we continue auditory evaluation of patients with autoinflammatory disorders, including Muckle Wells syndrome and neonatal onset autoinflammatory disorder (NOMID). We have completed gathering data at a 10-year time point post initiation of treatment with anakinra in a large group of patients with NOMID. A poster will be presented at the American College of Rheumatology (Alehashemi et al.) and manuscript is in preparation. 12. In collaboration with Dr. Heiss, we have examined vestibular function in persons with Chiari malformation and presented this work at the American Academy of Audiology meeting in March 2019 (Famili et al.). 13. In collaboration with Dr. Venditti, we have extensively examined the auditory phenotype of persons with methylmalonic acidemia and have a manuscript in development (Zalewski et al., in preparation) 14. In collaboration with Dr. Chittiboina (NINDS), we continue examination of auditory and vestibular function and longitudinal progression in patients with neurofibromatosis type 2 (NF2), a cause of hereditary hearing loss. We have a manuscript in development examining the ability of MRI to predict hearing loss in persons with NF2 (Walker et al., in preparation) 15. In addition to the areas listed above, the Audiology Unit participates in a number of research protocols in which we are conducting deep phenotyping of the auditory and vestibular systems. We are interested in the natural history of hearing loss and vestibular dysfunction, and relationships to other aspects of the disease/disorder and genotype. Our current areas of study include Batten disease/CLN3 (Dang Do, NICHD), congenital disorders of glycosylation (Wolfe & Gahl, NHGRI), gangliosidosis types 1 and 2 (Tifft, NHGRI), GATA2 (Holland, NIAID), hypogonadotropic hypogonadism (Freedman-Delaney, NICHD), Loeys Dietz syndrome (Guerrerio, NIAID), McCune Albright Syndrome (Boyce, NIDCR), oculocutaneous albinism (Adams, NHGRI), osteogenesis imperfecta (Marini, NICHD), propionic acidemia (Venditti, NHGRI), relapsing polychrondritis (Colbert, NIAID), spinocerebellar ataxia (SCA7) (Huryn, NEI), sex-chromosome variants (Muenke, NHGRI), von Hippel-Lindau disease (Heiss, NINDS), and xeroderma pigmentosum (Kraemer & Digiovanna, NCI). 16. We are examining auditory and vestibular function in patients who have experienced potential trauma to the auditory and vestibular systems, including repeated breacher explosions (Wasserman & LoPresti, NINDS; poster presented at Walter Reed conference) and traumatic brain injury (Chan, CC). 17. We contribute to the clinical characterization of auditory function, as indicated by presentation, of participants in the Undiagnosed Diseases Program (Gahl, NHGRI) and provide supportive clinical consultations to patients participating in multiple other protocols at the NIH Clinical Center.